The mechanism of hypertension's protective effect on dementia and slow gait in the oldest-old

 应聘者描述(由申请人提供)：应聘者是一名内科科学家，同时也是一名专门从事老年神经病学的委员会认证的神经科医生。在这个以患者为导向的导师职业发展奖中提出的培训和研究计划将推动候选人走向学术独立。这一奖项将支持她对高血压对90岁及以上老人步态缓慢和痴呆症的保护作用的研究。她将获得动脉僵硬(AS)和脑血流量(CBF)的非侵入性测量方面的专业知识，并将完成一个非全日制公共卫生硕士项目，这将为她的长期目标做好准备：为针对老年Cognitiv和身体损害的公共卫生预防努力做出贡献。应聘者在老年神经学、流行病学和心脏病学方面的专业知识将得到加强，因为该应用程序专注于与年龄相关的血管变化在老年痴呆和步态缓慢中的作用。此外，该奖项的拟议目标将为更大规模的研究申请(例如R01)奠定基础，并确保申请者朝着学术独立的方向发展。环境加州大学欧文分校提供一系列独特的培训和发展资源，帮助候选人晋升为独立的、学术的内科科学家职位。这些包括神经内科和记忆受损和神经疾病研究所的支持性教席和由杰出教员组成的团队，由导师(Claudia Kawas博士)、共同导师(Nathan Wong博士)和合作者(Michael Yassa博士)组成的杰出团队，接触到美国最大的特征最老的研究对象(90+研究)，最先进的神经成像设备，以及在整个奖项有效期内加速申请者职业发展的各种课程和研讨会。研究。高血压(HTN)与年轻老年人患痴呆症和步态缓慢的风险增加有关。然而，HTN似乎对年龄最大的老年人具有保护作用。这种保护作用的机制尚不清楚，也不能用治疗HTN或其他医学并发症的药物来解释。候选人假设，年龄最大的老年人的HTN代表了一种生理代偿机制，以在面临与年龄相关的动脉僵硬(AS)时保持足够的脑血流灌注。AS的患病率随着年龄的增长而增加，在较年轻的老年人中与痴呆症和步态缓慢有关。因此，特定的目标1试图确定AS与痴呆症和步态缓慢之间的关联是否因年龄最大的老年人中HTN的存在而不同。脑血流(CBF)随着AS和HTN的改变而改变，因此特定目标2的目的是确定高血压对痴呆和步态缓慢的保护作用是否可以解释最年长的老年人的CBF。最后，具体目标3试图确定AS和CBF之间的关联是否因年龄最大的老年人的HTN状态而不同。这些数据将直接有助于针对老年痴呆和步态缓慢的公共卫生努力，并可能为为高龄老年人制定特定年龄的HTN管理指南提供理论基础。

 DESCRIPTION (provided by applicant): The candidate is a physician scientist and a board-certified neurologist specializing geriatric neurology. The training and research plan proposed in this Mentored Patient-Oriented Career Development Award will propel the candidate toward academic independence. This award will support her investigation of the protective effect of hypertension on slow gait and dementia in the oldest-old; people aged 90 and older. She will gain expertise in the non-invasive measurement of arterial stiffness (AS) and cerebral blood flow (CBF) and will complete a part-time Master in Public Health program that will prepare her for her long-term goal: to contribute to the public health prevention efforts that target late-age cognitiv and physical impairment. The candidate's expertise in geriatric neurology, epidemiology and cardiology will be strengthened by the application's focus on the role of age-associated vascular changes in late-age dementia and slow gait. Furthermore, the proposed goals of the award will lay the foundation of a larger scale research application (e.g., R01) and ensure the applicant's development towards academic independence. Environment. The University of California, Irvine offers a unique array of training and development resources to facilitate the candidate advancing to an independent, academic physician scientist position. These include a supportive Chair and a collaborative group of distinguished faculty in the Department of Neurology and at the Institute for Memory Impairments and Neurological Disorders, an exceptional team of mentor (Dr. Claudia Kawas), co-mentor (Dr. Nathan Wong), and collaborator (Dr. Michael Yassa), access to the largest cohort of well-characterized oldest-old subjects in the USA (The 90+ Study), state-of-the-art neuroimaging facilities, and a variety of courses and workshops that will accelerate the applicant's career development throughout the duration of this award. Research. Hypertension (HTN) is associated with increased risk of dementia and slow gait in younger elderly. However, HTN appears to be protective in the oldest-old. The mechanism of this protective effect is unknown, and not explained by the use of medications for HTN or other medical comorbidities. The Candidate hypothesizes that HTN in the oldest-old represents a physiological compensatory mechanism to maintain adequate cerebral perfusion in the face of age-associated arterial stiffness (AS). The prevalence of AS increases with age, and in younger elderly AS is associated with dementia and slow gait. Therefore, Specific Aim 1 seeks to determine if the association between AS and dementia and slow gait varies by the presence of HTN in the oldest-old. Cerebral perfusion (CBF) changes with AS and HTN, thus the goal of Specific Aim 2 is to determine if the protective effect of hypertension on dementia and slow gait is explained by CBF in the oldest-old. Lastly, Specific Aim 3 seeks to determine if the association between AS and CBF varies by HTN status in the oldest-old. These data will directly contribute to the public health efforts that target late-age dementia and slow gait, and may also provide rationale for the development of age-specific HTN management guidelines for the oldest-old.